One hour after administration to phenobarbital (PB) pretreated rats the various halocarbons (3.73 mmole/kg i.p.) depleted hepatic glutathione (GSH) as follows: CHCl3, 75% CBrCl3, 41% CCl4 12%. All of these halocarbons were converted to GSCOSG when they incubated for 10 min in air with rat liver microsomes from PB-pretreated rats and GSH. This derivative of GSH was also identified as a metabolite in bile in the living rat. Moreover, the relative amounts of formation of GSCOSG paralleled the GSH depleting activities of the various halocarbons. These results indicate that GSCOSG is formed by the oxidative metabolism of the trihalo (CHX3) and tetrahalomethanes (CX4) into potentially toxic carbonyl halides (COX2) which are detoxified by their reaction with GSH to produce GSCOSG.